The overall goal of this molecular genetic project is to assess gene?environment interactions that may influence individual susceptibility to the EDs and developmental neurotoxicants that are the overall scientific theme of this Center. The plan is to meet this objective by identifying and characterizing polymorphisms and variations in expression levels of PON1, lipase and UGT-glucuronosyltransferase, all involved in the metabolism and detoxification of EDs and pesticides. The specific aims of this application are, Phthalates: 1) examine salivary lipase activity as a biomarker for conversion of phthalate diesters to phthalate monoesters; 2) determine expression levels of the three linked human lipase genes in human salivary glands; 3) determine racial/ethnic differences in the frequencies of the common polymorphisms in the salivary human lipase gene(s) and in salivary lipase activity; 4) examine salivary lipase activity in relation to urinary levels of phthalate metabolites; 5) examine salivary lipase polymorphisms and haplotypes in relation to urinary levels of phthalate metabolites; 6) obtain pilot data on the extent of glucuronidation of phthalate monoesters in urine; and 7) collaborate with the epidemiology project (Project 2) to examine association of lipase genotype and phenotype with child developmental outcomes. Bisphenol A: 1) genotype the common missense polymorphism in human UGT2B7 in our population of African-Americans, Caucasians and Hispanics and its association with urinary metabolites; 2) identify and assess common promoter, coding region and splice-site polymorphisms in human UGT2B7 in our African-Americans, Caucasians and Hispanics, establish the common haplotypes, and their association with exposure; and 3) collaborate with Project 2 to examine human UGT2B7 genotype/haplotype effects on developmental outcomes. Continuing PON1 phenotype?genotype studies: 1) determine high-density lipid (HDL) levels for the existing birth cohort and carry out a detailed genotype?phenotype reanalysis, 2) genotype and haplotype new members of the extended birth cohort for PON1 polymorphisms; and 3) collaborate with Project 2 to examine PON1 genotype and phenotype effects on developmental outcomes.